Quantification of diffusion tensor imaging (DTI) parameters has become an important role in the neuroimaging, neurosurgical, and neurological community as a method to identify major white matter tracts afflicted by pathology or tracts at risk for a given surgical approach. We introduce a novel framework for a reliable and robust quantification of DTI parameters, which overcomes problems of existing techniques introduced by necessary user inputs. In a first step, a hybrid clustering method is proposed that allows for extracting specific fiber bundles in a robust way. Compared to previous methods, our approach considers only local proximities of fibers and is insensitive to their global geometry. This is very useful in cases where a fiber tracking of the whole brain is not available. Our technique determines the overall number of clusters iteratively using a eigenvalue thresholding technique to detect disjoint clusters of independent fiber bundles. Afterwards, possible finer substructures based on an eigenvalue regression are determined within each bundle. In a second step, a quantification of DTI parameters of the extracted bundle is performed. We propose a method that automatically determines a 3D image where the voxel values encode the minimum distance to a reconstructed fiber. This image allows for calculating a 3D mask where each voxel within the mask corresponds to a voxel that lies in an isosurface around the fibers. The mask is used for an automatic classification between tissue classes (fiber, background, and partial volume) so that the quantification can be performed on one or more of such classes. This can be done per slice or a single DTI parameter can be determined for the whole volume which is covered by the isosurface. Our experimental tests confirm that major white matter fiber tracts may be robustly determined and can be quantified automatically. A great advantage of our framework is its easy integration into existing quantification applications so that uncertainties can be reduced, and higher intrarater- as well as interrater reliabilities can be achieved.